CaMKIIα-GluA1 Activity Underlies Vulnerability to Adolescent Binge Alcohol Drinking.
Alcohol Clin Exp Res
; 39(9): 1680-90, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-26247621
ABSTRACT
BACKGROUND:
Binge drinking during adolescence is associated with increased risk for developing alcohol use disorders; however, the neural mechanisms underlying this liability are unclear. In this study, we sought to determine whether binge drinking alters expression or phosphorylation of 2 molecular mechanisms of neuroplasticity, calcium/calmodulin-dependent kinase II alpha (CaMKIIα) and the GluA1 subunit of AMPA receptors (AMPARs) in addiction-associated brain regions. We also asked whether activation of CaMKIIα-dependent AMPAR activity escalates binge-like drinking.METHODS:
To address these questions, CaMKIIαT286 and GluA1S831 protein phosphorylation and expression were assessed in the amygdala and striatum of adolescent and adult male C57BL/6J mice immediately after voluntary binge-like alcohol drinking (blood alcohol >80 mg/dl). In separate mice, effects of the CaMKIIα-dependent GluA1S831 phosphorylation (pGluA1S831 )-enhancing drug tianeptine were tested on binge-like alcohol consumption in both age groups.RESULTS:
Binge-like drinking decreased CaMKIIαT286 phosphorylation (pCaMKIIαT286 ) selectively in adolescent amygdala with no effect in adults. Alcohol also produced a trend for reduced pGluA1S831 expression in adolescent amygdala but differentially increased pGluA1S831 in adult amygdala. No effects were observed in the nucleus accumbens or dorsal striatum. Tianeptine increased binge-like alcohol consumption in adolescents but decreased alcohol consumption in adults. Sucrose consumption was similarly decreased by tianeptine pretreatment in both ages.CONCLUSIONS:
These data show that the adolescent and adult amygdalae are differentially sensitive to effects of binge-like alcohol drinking on plasticity-linked glutamate signaling molecules. Tianeptine-induced increases in binge-like drinking only in adolescents suggest that differential CaMKIIα-dependent AMPAR activation may underlie age-related escalation of binge drinking.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de AMPA
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Etanol
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina
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Consumo Excessivo de Bebidas Alcoólicas
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Tonsila do Cerebelo
Limite:
Animals
Idioma:
En
Revista:
Alcohol Clin Exp Res
Ano de publicação:
2015
Tipo de documento:
Article
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM